Low P300 amplitudes and topographical asymmetries have been reported in schizophrenic patients, but reference-independent amplitude assessment failed to replicate reduced amplitudes. P300 amplitude is conventially assessed at midline electrodes (Pz), and asymmetric topography as reported in schizophrenics, may confound this measurement. We investigated the possible interaction between P300 topography and assessments of amplitudes. In 41 clinically stable schizophrenics and 31 normal controls, the general finding of reduced amplitudes at the Pz-electrode and topographical asymmetries in the patient group were replicated. In both groups, asymmetries of the P300 field (lateralized peaks) reduced the standard amplitude assessment at the midline parietal electrode, but did not affect the reference-independent, global amplitude assessment. This shows that asymmetry per se does not imply reduced field strength. In addition, in schizophrenics, but not in controls, there was a significant effect of the direction of asymmetry on both amplitude measures, amplitudes being lower with increasing shift of the P300 peak to the right side. Considering also the slightly left-lateralized peaks in the normal controls, this suggests that only right-lateralized P300 peaks express functional deficits in schizophrenics, whereas left-lateralized peaks fall within the physiological variability of the P300 field. The reference-independent amplitude assessment is proposed for unambiguous amplitude assessment in order to better define the clinical, psychological and physiopathological meaning of the P300 alterations in schizophrenics.